scholarly journals Early loss of Scribble affects cortical development, interhemispheric connectivity and psychomotor activity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jerome Ezan ◽  
Maité M. Moreau ◽  
Tamrat M. Mamo ◽  
Miki Shimbo ◽  
Maureen Decroo ◽  
...  
Keyword(s):  
Planar Cell Polarity ◽  
Gene Mutations ◽  
Cellular Mechanisms ◽  
Activity Impairment ◽  
Psychomotor Activity ◽  
Mouse Mutants ◽  
Interhemispheric Connectivity ◽  
Evolutionarily Conserved ◽  
And Behavior ◽  
The Impact

AbstractNeurodevelopmental disorders arise from combined defects in processes including cell proliferation, differentiation, migration and commissure formation. The evolutionarily conserved tumor-suppressor protein Scribble (Scrib) serves as a nexus to transduce signals for the establishment of apicobasal and planar cell polarity during these processes. Human SCRIB gene mutations are associated with neural tube defects and this gene is located in the minimal critical region deleted in the rare Verheij syndrome. In this study, we generated brain-specific conditional cKO mouse mutants and assessed the impact of the Scrib deletion on brain morphogenesis and behavior. We showed that embryonic deletion of Scrib in the telencephalon leads to cortical thickness reduction (microcephaly) and partial corpus callosum and hippocampal commissure agenesis. We correlated these phenotypes with a disruption in various developmental mechanisms of corticogenesis including neurogenesis, neuronal migration and axonal connectivity. Finally, we show that Scrib cKO mice have psychomotor deficits such as locomotor activity impairment and memory alterations. Altogether, our results show that Scrib is essential for early brain development due to its role in several developmental cellular mechanisms that could underlie some of the deficits observed in complex neurodevelopmental pathologies.

scholarly journals Early loss of Scribble affects cortical development and interhemispheric connectivity resulting in psychomotor dysregulation

2019 ◽  
Author(s):  
Jerome Ezan ◽  
Maité M. Moreau ◽  
Tamrat M. Mamo ◽  
Miki Shimbo ◽  
Maureen Decroo ◽  
...  
Keyword(s):  
Planar Cell Polarity ◽  
Gene Mutations ◽  
Axonal Guidance ◽  
Activity Impairment ◽  
Mouse Mutants ◽  
Interhemispheric Connectivity ◽  
Evolutionarily Conserved ◽  
Early Brain Development ◽  
And Behavior ◽  
The Impact

AbstractNeurodevelopmental disorders arise from combined defects in processes including cell proliferation, differentiation, migration and commissure formation. The evolutionarily conserved tumor-suppressor protein Scribble (Scrib) serves as a nexus to transduce signals for the establishment of apicobasal and planar cell polarity during these processes. Human SCRIB gene mutations are associated with neural tube defects and this gene is located in the minimal critical region deleted in the rare Verheij syndrome. In this study, we generated brain-specific conditional cKO mouse mutants and assessed the impact of the Scrib deletion on brain morphogenesis and behavior. We showed that embryonic deletion of Scrib in the telencephalon leads to cortical thickness reduction (microcephaly) and alteration of interhemispheric connectivity (corpus callosum and hippocampal commissure agenesis). We correlated these phenotypes with the identification of novel roles for Scrib, both cell- and non-cell-autonomous, on neuronal migration and axonal guidance respectively. Finally, we show that Scrib cKO mice have psychomotor deficits such as locomotor activity impairment and memory alterations. Altogether, we show that Scrib is essential for early brain development and that the outcomes of its brain-specific disruption support a direct or indirect participation of Scrib to neurodevelopmental pathologies.

Interpreting Neonatal Lethal Phenotypes in Mouse Mutants: Insights Into Gene Function and Human Diseases

2009 ◽  
Vol 89 (1) ◽  
pp. 1-26 ◽  
Author(s):  
Benjamin Turgeon ◽  
Sylvain Meloche
Keyword(s):  
Gene Function ◽  
Gene Mutations ◽  
Mutant Mice ◽  
Human Diseases ◽  
Mouse Development ◽  
Phenotypic Analysis ◽  
Mouse Mutants ◽  
Physiological Processes ◽  
Neonatal Lethality ◽  
The Impact

The mouse represents the model of choice to study the biological function of mammalian genes through mutation of its genome. However, the biggest challenge of mouse geneticists remains the phenotypic analysis of mouse mutants. A survey of mouse mutant databases reveals a surprisingly high number of gene mutations leading to neonatal death. These genetically modified mouse mutants have been instrumental in elucidating gene function and have become important models of congenital human diseases. The main complication when phenotyping mutant mice dying during the neonatal period is the large spectrum of physiological systems whose defects can challenge neonatal survival. Here, we present a comprehensive review of gene mutations leading to neonatal lethality and discuss the impact of these mutations on the major physiological processes critical to mouse newborn survival: parturition, breathing, suckling, and homeostasis. Selected examples of mouse mutants are highlighted to illustrate how the precise identification of the timing and cause of death associated with these physiological processes allows for a more profound understanding of the underlying cellular and molecular defects. This review provides a guide for the analysis of neonatal lethal phenotypes in mutant mice that will be helpful for dissecting out the function of specific genes during mouse development.

The Impact of COVID-19 Quarantine on Children‘s Behaviors and Language

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 796-806
Author(s):  
Sana M Kamal ◽  
Ali Al-Samydai ◽  
Rudaina Othman Yousif ◽  
Talal Aburjai
Keyword(s):  
Social Relations ◽  
Child Psychology ◽  
Simple Random Sample ◽  
Community Pharmacies ◽  
The World ◽  
Female Children ◽  
And Behavior ◽  
The Impact ◽  
Pharmaceutical Interventions

COVID-19 pandemic has spread across the world, which considered a relative of the severe acute respiratory syndrome (SARS), with possibility of transmission from animals to human and effect each of health and economic. Several preventative strategies and non-pharmaceutical interventions have been used to slow down the spread of COVID-19. The questionnaire contained 36 questions regarding the impact of COVID-19 quarantine on children`s behaviors and language have been distributed online (Google form). Data collected after asking parents about their children behavior during quarantine, among the survey completers (n=469), 42.3% were female children, and 57.7 were male children. Results showed that quarantine has an impact on children`s behaviors and language, where stress and isolationism has a higher effect, while social relations had no impact. The majority of the respondents (75.0%) had confidence that community pharmacies can play an important role in helping families in protection their children`s behaviors and language as they made the highest contact with pharmacists during quarantine. One of the main recommendations that could be applied to help parents protection and improvement their children`s behaviors and language in quarantine condition base on simple random sample opinion is increasing the role of community pharmacies inpatient counseling and especially towards children after giving courses to pharmacists in child psychology and behavior. This could be helpful to family to protect their children, from any changing in them behaviors and language in such conditions in the future if the world reface such the same problem.

THE IMPACT OF "PUBLIC CULTURE" ON YOUTH SPIRITUALITY

2020 ◽  
Vol 3 (1) ◽  
pp. 130-135
Author(s):  
Mukhiddin Tursunmuratov ◽  
Keyword(s):  
Popular Culture ◽  
Young People ◽  
Public Culture ◽  
And Behavior ◽  
The Impact

This article provides a detailed description and explanation of the term "popular culture". It also analyzes a number of aspects of "popular culture" that are becoming more widespread today, their role and influence in the formation of the minds and behavior of young people, and draws the necessary conclusions. Most importantly, it also describes ways to protect young people from threats in the form of "popular culture" that negatively affect their morale.

Understanding Motivating Operations and the Impact on the Function of Behavior

2020 ◽  
Vol 56 (2) ◽  
pp. 119-122
Author(s):  
Doris Adams Hill ◽  
Theoni Mantzoros ◽  
Jonté C. Taylor
Keyword(s):  
Behavioral Interventions ◽  
Special Educators ◽  
Motivating Operations ◽  
Behavior Intervention Plans ◽  
Education Professionals ◽  
Functional Behavior ◽  
Special Education Professionals ◽  
And Function ◽  
And Behavior ◽  
The Impact

Special educators are often considered the experts in their school when it comes to developing functional behavior assessments (FBA) and behavior intervention plans (BIP), yet rarely are they trained much beyond basic antecedents, behaviors, and consequences (ABC). This column discusses concepts that will expand special education professionals’ knowledge to make better decisions regarding interventions for the students they serve. Specifically, the focus is on motivating operations (MO) and function-based interventions and the implications of these on behavior. Knowledge of the concept of MOs can enhance a teacher’s ability to provide evidence-based interventions and more fully developed behavioral interventions for students in their purview.

A Melanocortin-4 Receptor Agonist Induces Skin and Hair Pigmentation in Patients with Monogenic Mutations in the Leptin-Melanocortin Pathway

2021 ◽  
pp. 1-10
Author(s):  
Varvara Kanti ◽  
Lia Puder ◽  
Irina Jahnke ◽  
Philipp Maximilian Krabusch ◽  
Jan Kottner ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Skin Pigmentation ◽  
Gene Mutations ◽  
Continuous Treatment ◽  
Whole Body ◽  
Hair Color ◽  
Phase 2 ◽  
Loss Of Function ◽  
The Impact ◽  
Over Time

<b><i>Background and Objectives:</i></b> Gene mutations within the leptin-melanocortin signaling pathway lead to severe early-onset obesity. Recently, a phase 2 trial evaluated new pharmacological treatment options with the MC4R agonist <i>setmelanotide</i> in patients with mutations in the genes encoding proopiomelanocortin (POMC) and leptin receptor (LEPR). During treatment with <i>setmelanotide,</i> changes in skin pigmentation were observed, probably due to off-target effects on the closely related melanocortin 1 receptor (MC1R). Here, we describe in detail the findings of dermatological examinations and measurements of skin pigmentation during this treatment over time and discuss the impact of these changes on patient safety. <b><i>Methods:</i></b> In an investigator-initiated, phase 2, open-label pilot study, 2 patients with loss-of-function POMC gene mutations and 3 patients with loss-of-function variants in LEPR were treated with the MC4R agonist <i>setmelanotide</i>. Dermatological examination, dermoscopy, whole body photographic documentation, and spectrophotometric measurements were performed at screening visit and approximately every 3 months during the course of the study. <b><i>Results:</i></b> We report the results of a maximum treatment duration of 46 months. Skin pigmentation increased in all treated patients, as confirmed by spectrophotometry. During continuous treatment, the current results indicate that elevated tanning intensity levels may stabilize over time. Lips and nevi also darkened. In red-haired study participants, hair color changed to brown after initiation of <i>setmelanotide</i> treatment. <b><i>Discussion:</i></b> <i>Setmelanotide</i> treatment leads to skin tanning and occasionally hair color darkening in both POMC- and LEPR-deficient patients. No malignant skin changes were observed in the patients of this study. However, the results highlight the importance of regular skin examinations before and during MC4R agonist treatment.

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